Heart Failure With Preserved Ejection Fraction
Conditions
Brief summary
Beta blockers have been used to reduce the mortality and heart failure rehospitalization in heart failure with reduced ejection fraction (HFrEF) patients in addition to ACEI/ARB, MRA, ivabradine and ARNI. However, the effective and safe medical therapy is not well established in heart failure with preserved ejection fraction (HFpEF) yet. Recent meta-analysis showed that beta blockers may also be beneficial for reducing the mortality and heart failure rehospitalization in HFpEF like HFrEF. However, the clinical effect and safety of carvedilol have been largely unknown in HFpEF. Therefore, CAYMUS HFpEF is the exploratory study to assess the change of surrogate markers (NTproBNP, hsTn) when treated with carvedilol SR vs. placebo in HFpEF patients
Interventions
DRUGCarvedilol SR
blood pressure, heart rate based titrated carvedilol SR for 24 weeks
DRUGPlacebo
Placebo
Sponsors
Yonsei University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Carvedilol SR vs. Placebo
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Provision of informed consent prior to any study specific procedure 2. Male or female, aged ≥ 19 years 3. Patients with chronic HF (Chronic Heart Failure) NYHA (New York Heart Association classification) class II-IV and preserved EF (Ejection Fraction)(LVEF (Left Ventricular Ejection Fraction) \> 40 %) and elevated NT-proBNP (N-terminal of the prohormone brain natriuretic peptide) \> 200 pg/ml for patients without AF, OR \> 600 pg/ml for patients with AF, analysed at the Central laboratory at Visit 1 4. Structural heart disease within 6 months prior to Visit 1 using echocardiagraphy
Exclusion criteria
1. Myocardial infarction, coronary artery bypass graft surgery or other major cardiovascular surgery, stroke or TIA (Transient Ischaemic Attack) in past 90 days prior to Visit 1 2. Contraindication to beta blocker 3. Heart transplant recipient or listed for heart transplant 4. Hospitalization plan for PCI, coronary artery bypass graft surgery, other cardiac invasive interventions (e.g. catheter ablation, pacemaker, CRT, ICD implantation) 5. Acute decompensated HF (Heart Failure) 6. Symptomatic hypotension or systolic blood pressure \< 100 mmHg) 7. Patients with CrCl \< 30 ml/min using creatinine-based CKD-EPI equations 8. Elevated liver enzymes (3 times over upper reference limit) or liver cirrhosis 9. Symptomatic bradycardia or heart rate \< 60/min 10. Allergy, adverse drug reaction, hypersensitivity to carvedilol 11. Life expectancy \< 6 months (e.g. metastatic malignancy) 12. Pregnancy, or women of childbearing age
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Maximum NT-proBNP value change after Drug(Carvedilol SR or Placebo) administration. | Baseline | The maximum NT-proBNP value change at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| all-cause hospitalization & mortality | Baseline | all-cause hospitalization & mortality during the trial |
| The changes of maximum surrogate markers values(hsTn, hsCRP, sST2, Galectine-3, IGFBP7, Neprilysin, D-dimer, MMP-2, Cystatin C, NAG, NGAL, KIM-1, BUN, Creatinine, Chloride, Na, K, PICP and spondin-1) after Drug(Carvedilol SR or Placebo) administration. | Baseline | the change of surrogate markers(hsTn, hsCRP etc) at baseline. |
| the frequency of hypo/hyperkalemia and worsening kidney function | Baseline | the frequency of hypo/hyperkalemia and worsening kidney function during the trial |
| the change of body weight | Baseline | the change of body weight at baseline. |
| the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree | Baseline | the frequency of symptomatic hypotension, symptomatic bradycardia and AV block above 2nd degree during the tiral |
| The change in degree of dyspnea using VAS questionnaire | Baseline | the change of dyspnea at baseline. |
Countries
South Korea
Contacts
Primary ContactSeok-Min Kang, MD, Ph.D
Outcome results
None listed